Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive.
Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP. A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00117/full |
| _version_ | 1818519759449227264 |
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| author | Sébastien eLaurent Adrien eRichard Odile eMulner-Lorillon Odile eMulner-Lorillon Julia eMorales Julia eMorales Didier eFlament Virginie eGlippa Virginie eGlippa Jérémie eBourdon Pauline eGosselin Pauline eGosselin Anne eSiegel Anne eSiegel Patrick eCormier Patrick eCormier Robert eBellé Robert eBellé |
| author_facet | Sébastien eLaurent Adrien eRichard Odile eMulner-Lorillon Odile eMulner-Lorillon Julia eMorales Julia eMorales Didier eFlament Virginie eGlippa Virginie eGlippa Jérémie eBourdon Pauline eGosselin Pauline eGosselin Anne eSiegel Anne eSiegel Patrick eCormier Patrick eCormier Robert eBellé Robert eBellé |
| author_sort | Sébastien eLaurent |
| collection | DOAJ |
| description | Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP. A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in the total 4E-BP amount observed during time after fertilization. Our study evidenced that two changes occurring at fertilization are necessary to fit with experimental data. The first change was an 8 fold increase in the dissociation parameter (koff1) of the eIF4E:4E-BP complex. The second was an important 32.5 fold activation of the degradation mechanism of the protein 4E-BP. Additionally, the changes in both processes should occur in five minutes time interval post fertilization. To validate the model, we checked that the kinetic of the predicted 4.2 fold increase of eIF4E:eIF4G complex concentration at fertilization matched the increase of protein synthesis experimentally observed after fertilization (6.6 fold, SD=2.3, n=8). <br/>The minimal model was also used to simulate changes observed after fertilization in the presence of rapamycin, a FRAP/mTOR inhibitor. The model showed that the eIF4E:4E-BP complex destabilization was impacted and, surprisingly, that the mechanism of 4E-BP degradation was also strongly affected, therefore suggesting that both processes are controlled by the protein kinase FRAP/mTOR. <br/> |
| first_indexed | 2024-12-11T01:28:21Z |
| format | Article |
| id | doaj.art-b48e1c46e4ca4a3882aed00516ae5062 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T01:28:21Z |
| publishDate | 2014-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b48e1c46e4ca4a3882aed00516ae50622022-12-22T01:25:27ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-05-01510.3389/fgene.2014.0011787723Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive.Sébastien eLaurent0Adrien eRichard1Odile eMulner-Lorillon2Odile eMulner-Lorillon3Julia eMorales4Julia eMorales5Didier eFlament6Virginie eGlippa7Virginie eGlippa8Jérémie eBourdon9Pauline eGosselin10Pauline eGosselin11Anne eSiegel12Anne eSiegel13Patrick eCormier14Patrick eCormier15Robert eBellé16Robert eBellé17Ifremer, UMR6197Université de Nice-Sophia AntipolisSorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227Sorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227Ifremer, UMR6197Sorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227CNRS, UMR 6241Sorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227CNRS, IRISA-UMR 6074INRIA, Centre Rennes – Bretagne AtlantiqueSorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227Sorbonne Universités, UPMC Univ Paris 06, UMR 8227CNRS, UMR 8227Fertilization of sea urchin eggs involves an increase in protein synthesis associated with a decrease in the amount of the translation initiation inhibitor 4E-BP. A highly simple reaction model for the regulation of protein synthesis was built and was used to simulate the physiological changes in the total 4E-BP amount observed during time after fertilization. Our study evidenced that two changes occurring at fertilization are necessary to fit with experimental data. The first change was an 8 fold increase in the dissociation parameter (koff1) of the eIF4E:4E-BP complex. The second was an important 32.5 fold activation of the degradation mechanism of the protein 4E-BP. Additionally, the changes in both processes should occur in five minutes time interval post fertilization. To validate the model, we checked that the kinetic of the predicted 4.2 fold increase of eIF4E:eIF4G complex concentration at fertilization matched the increase of protein synthesis experimentally observed after fertilization (6.6 fold, SD=2.3, n=8). <br/>The minimal model was also used to simulate changes observed after fertilization in the presence of rapamycin, a FRAP/mTOR inhibitor. The model showed that the eIF4E:4E-BP complex destabilization was impacted and, surprisingly, that the mechanism of 4E-BP degradation was also strongly affected, therefore suggesting that both processes are controlled by the protein kinase FRAP/mTOR. <br/>http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00117/fulltranslational controlsea urchin embryosmechanisms of fertilizationdeterministic modeltranslation simulation |
| spellingShingle | Sébastien eLaurent Adrien eRichard Odile eMulner-Lorillon Odile eMulner-Lorillon Julia eMorales Julia eMorales Didier eFlament Virginie eGlippa Virginie eGlippa Jérémie eBourdon Pauline eGosselin Pauline eGosselin Anne eSiegel Anne eSiegel Patrick eCormier Patrick eCormier Robert eBellé Robert eBellé Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. Frontiers in Genetics translational control sea urchin embryos mechanisms of fertilization deterministic model translation simulation |
| title | Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. |
| title_full | Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. |
| title_fullStr | Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. |
| title_full_unstemmed | Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. |
| title_short | Modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes: a destabilization of eIF4E:4E-BP complex and a great stimulation of the 4E-BP-degradation mechanism, both rapamycin-sensitive. |
| title_sort | modelisation of the regulation of protein synthesis following fertilization in sea urchin shows requirement of two processes a destabilization of eif4e 4e bp complex and a great stimulation of the 4e bp degradation mechanism both rapamycin sensitive |
| topic | translational control sea urchin embryos mechanisms of fertilization deterministic model translation simulation |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00117/full |
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